Local Anesthetics Flashcards
What are local anesthetic used for?
they are used to reversibly block nerve conduction in a particular region of the body
What are all LA’s analogs of?
cocaine
What are the methods of local anesthetic administration (5)?
topical administration, infiltration, nerve block, spinal block, epidural block
What’s unique about cocaine (4)?
administered topically, goes through mucosal membranes, used for EENT, causes vasoconstriction
In what form can LA’s penetrate membranes?
in the unionized form
What sort of analgesia can spinal block produce?
regional (as well as local)
What are the thee parts that make up the structure of LA’s?
ionizable “head”, an amide or ester containing connecting chain, and a non-polar “tail” usually containing a phenyl ring.
Are clinically used LA’s acidic or basic?
weak bases usually containing a tertiary amino group as hydrophilic, cationic group
What are the ester type drugs (4)?
cocaine, procaine, benzocaine, tetracaine
What are the amine type drugs (3)?
lidocaine, Mepivacaine (R=methyl), Bupivacaine (R=butyl)
What’s unique about benzocaine?
low water solubility and less polar, so can’t be injected and is instead used topically (often an ingredient in after sun lotions)
Which type have a greater vasodilatory effect?
I think he said ester type…? but of course not cocaine
What’s unique about Tetracaine?
very lipophilic, one of the most potent, long duration of action. limited to spinal injection
What’s unique about bupivacaine?
spinal injection, lipphilic, long-acting, potent, CARDIOTOXIC
What’s unique about mepivacaine?
advantage over lidocaine = less adverse effects
What’s special about Lidocaine?
prototype of amide types
What’s special about procaine?
=Novacane, large vasodilatory effect
How do LA’s work?
they preferentially block voltage-dependent sodium channels in nerve and muscle membranes. “lipid route” on extracellular fluid side, “polar” route on intracellular fluid side
What is the relationship between intensity of local anesthesia and spike frequency? Why?
intensity increases with spike frequency because the opened and inactivated states of the sodium channel, which bind the LA most readily, are occupied a greater fraction of the time,
upon which cells are LA’s most effective?
active cells.
Which is more lipophilic- bupivacaine or lidocaine?
bupivacaine
Why does bupivacaine modify the normal cardiac rhythm?
block by bupivacaine occurs in the normal frequency range of the myocardium.
What does Lidocaine selectively block and why?
tachycardias, because it only displays its maximal blocking activity at much higher than normal beat frequencies.
What is the major toxicity of bupivacaine? why?
cardiotoxicity due to its slow rate of dissociation from the myocardial sodium channel
Which form most rapidly penetrates the sheath and plasma membranes?
the unionized form
Which form is most active in blocking the sodium channel?
the cationic amine form
Since bupivacaine and lidocaine both have frequency-dependent block of sodium channels, what can they be used for?
antiepileptic in brain and antiarrhythmic in heart
What is one major problem with LA’s and what accentuates is?
Vascular absorption- this problem is accentuated by the vasodilatory actions of all LAs except for cocaine.
What can be added to slow vascular absorption? what does this do?
vasoconstrictors like epinephrine. this increased the rate and intensity of nerve block and prolongs the duration of action.
What does reduced plasma LA concentration mean? what’s up with newer LAs?
fewer systemic complications. newer LAs produce less vasodilation
What can happen when LAs are incorrectly injected or absorbed too rapidly?
systemic toxicity! CNS convulsion and depression (leading to respiratory depression) may occur.
What are the pharmacological antagonists for systemic toxicity?
there are none! treatment includes artificial respiration with pure oxygen and administration of anticonvulsant (Valium)
What is the relationship between Lidocaine plasma concentration and its pharmacological effects?
anti-arrhythmic at very low doses…circumoral and tongue numbness…lightheadedness, tinnitus…visual disturbances…muscular twitching…convulsions…coma…respiratory arrest…cardiovascular depression
How are ester LAs metabolized?
they are hydrolyzed by plasma (non-specific) cholinesterase
How are amide LAs metabolized?
they are dealkylared and hydrolyzed in the liver
What is the major factor in determining the duration of local anesthesia?
vascular absorption
Why is metabolism important (2)?
Controlling a) the antiarrhythmic duration of action of procainamide and lidocaine and b) fetal CNS depression due to absorption of LA from mommy’s circulation
